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Therapeutics of stem cells in periodontal regeneration

Journal of Natural Science , Biology and Medicine , Jan 2011, Vol 2, Issue 1

Rajiv Saini et al

The structure and composition of the periodontium are affected in many acquired and hentable diseases and the most significant among these is periodontal diseases .periodontal regeneration is considered to be organically promising but clinically capricious. The principal requirements for tissue engineering are incorporation of appropriate numbers of responsive progenitor cells and the presence of bioactive levels of regulatory signals within an appropriate extracellular matrix or carrier construct. Stem tissues that are damaged And recent progress in stem cells research and in tissue engineering promises nowel prospects for therapeutic strategies for the replacement of a diseased or damaged tooth.


Intravenous Mesenchymal Stem Cells Prevented Rejection of Allogeneic Corneal Transplants by Aborting the Early Inflammatory Response

Molecular Therapy, (28 August 2012)|doi:10.1038/mt.2012.165

Joo Youn Oh, Ryang Hwa Lee, Ah Young Ko, Gavin W Roddy and Darwin J Prockop

Mesenchymal stem/progenitor cells (MSCs) were reported to enhance the survival of cellular and organ transplants. However, their mode of action was not established. We here used a mouse model of corneal allotransplantation and demonstrated that peri-transplant intravenous (i.v.) infusion of human MSCs (hMSCs) decreased the early surgically induced inflammation and reduced the activation of antigenpresenting cells (APCs) in the cornea and draining lymph nodes (DLNs). Subsequently, immune rejection was decreased , and allograft survival was prolonged. Quantitative assays for human GAPDH revealed that 10 hMSCs out of 1 x 106 injected cells were recovered in the cornea 10 hours to 28 days after i.v. infusion. Most of hMSCs were trapped in lungs where they were activated to increase expression of the gene for a multifunctional anti-inflammatory protein tumor necrosis factor-α stimulated gene/protein 6 (TSG-6). I.V. hMSCs with a knockdown of TSG-6 did not suppress the early inflammation and failed to prolong the allograft survival. Also, i.v. infusion of recombinant TSG-6 reproduced the effects of hMSCs. Results suggest that hMSCs improve the survival of corneal allografts without engraftment and primarily by secreting TSG-6 that acts by aborting early inflammatory responses. The same mechanism may explain previous reports that MSCs decrease rejection of other organ transplants.


High-purity hepatic differentiated from dental pulp stem cells in serum-free medium

J Endod 2012 Apr;38(4):475-80. Epub 2012 Jan28

INTRODUCTION: We have previously differentiated hepatocyte like cells from deciduoud tooth pulp stem and extracted third molar pulp stem cells with a protocol that used fetal bovine serum, but it showed high contaminations of nondifferentiated cells. Both the lower purity of hepatically differentiated cells and usage of serum are obstacles for applications of cell therapy or regenerative medicine. Objective of this study was to investigate the capacity for and purity of hepatocyte-like differentiation of CD 117-positive dental pulp stem cells without serum.

METHODS: Mesenchymal cells from human deciduous and extracted third molar pulp were isolated and expanded in vitro. We separated D117-position cells by using a magnetic-activated cell sorter. The cells were characterized immunofluorescently by using known stem cell markers. For hepatic differentiation, the media were supplemented with hepatic growth factor, insulin transferring-selenium-x, dexamethasone, and oncostatin M. Expression of hepatic markers alpha fetoprotein, albumin, hepatic nuclear factor-4 alpha, insulin-like growth factor-1, and carbamoyl phosphate synthetase was examined immunoflurescently after differentiation. The amount of differentiated cells was assessed by using flow cytometry. Glycogen storage and area concentration in the medium were defined.

RESULTS: Both cell cultures demonstrated a number of cells positive for all tested hepatic markers after differentiation,ie, albumin-positive cells were almost 90% of differentiated deciduous pulp cells. The concentration of urea in the media increased significantly after differentiation. Significant amount of cytoplasmic glycogen storage was found in the cells.

CONCLUSIONS: Without serum both cell types differentiated into high-purity hepatocyte-like cells. These cells offer a source for hepatocypte lineage differentiation for transplantation in the future.


Stem Cells in Regenerative Endodontics: A Review

Parul Mehta

Regenerative Endodontics is expected to become the next big treatment revolution. It is the creation and delivery of tissues to replace a diseased, missing and traumatized pulp dentin complex, in addition to tooth supporting tissues. It employs dental stem cells for this which is especially important because they are a type of mesenchymal stem cells that produce more neurotrophic factors than other cell types. These cells have demonstrated the ability to protect and repair neural tissue in diseases like spinal cord injury and stroke and hence can also be used for development of treatment solutions for such diseases. Dental stem cells are also easy to procure and preserve for use in future therapies.



Prespectives on Mesenchymal Stem Cell: Tissue Repair, Immune Modulation, and Tumor Homing

Arch Pharm Res Vo 35, No,2 201-211, 2012
DOT 10.1007 / s 12272-012-0201-0

Hyun Sook Hong, Yeong Hoon Kim, Youngsook Son

Mesenchymal stem cells (MSCs) or MSC – Like cells have been identified in a variety of different tissues that share molecular expression profiles and biological functions but also retain a unique differentiation preference depending on their tissue origins. MSCs play beneficial roles in the healing of damaged tissue by directly differentiating to many different resident cell types and / or by secreting several trophic factors that aid tissue repair. Aside from MSCs reparative stem cell function, they drive immune responses toward immunosuppression and anti - inflammation . This novel function of MSCs opens up new avenues for clinical development of MSC immune - therapeutics to treat uncontrollable, life threatening, severe , chronic inflammation and autoimmune disease.

MSCs or MSC – like cells, even though their tissue origins are different, are quite similar in expression of molecular markers and biological functions. MSCs are expected as reparative stem cell for a variety of tissue injuries or disease by differentiating to many different types of resident tissue cells. More frequently, life threatening steroid refractory immune rejection, and autoimmune syndrome, MSCs other novel function, an immune modulating effect, is adopted for the therapeutic rationale. However, in certain tumor setting, MSCs immune modulatory function, in combination with their tumor homing preference, may provide a reason for their causing unwanted tumor progression. This tumor homing capacity of MSCs can be strategically utilized as a novel tumor – targeting anticancer therapeutic. In conclusion, recent progress in MSCs therapeutics promises benefits for numerous uncontrolled diseases that cannot be met by conventional medication. Also their possible risk for the progression of tumors was uncovered. Therefore, MSC therapeutics can be advantageously developed as a specific tumor – targeting delivery vehicle.



Journal of Bone & Joint Surgery, British Volume
J Bone Joint Surg Br 2012 vol, 94-B no. SUPP XXXVI 43

NAL-Hazaimeh, J Beattle, M Duggal and XB Yang


Angiogenesis and the ability to provide appropriate vascular supply are crucial for skeletal tissue engineering. The aim of this study was to investigate the anglogenic potential (currently under experimental research) of human dental pulp stromal cells (HDPSCs) and stro-1 positive populations as well as their role in tissue regeneration ( the clinical reality).

HDPSC were isolated from the pulp tissue of human permanent teeth by collagenase digestion. STRO-1 positive cells were enriched using mono clonal anti STRO-1 and anti CD-45 PE conjugated anti bodies together with and fluorescence activated cell sorting (FACS). Cells isolated by FACS were grown to passage 4 and cultured as mono layers or on 3D matrigel scaffold in endothelial cell growth medium -2 (EGM_2) with/without 50ng/ml of vascular endothelial growth factor (VEGF). Cells cultured in alpha MEM supplemented with 10% FCS were used as controls. After 24, 48 and 72 hours anglogenic marker expression (CD31, CD34, vWF and VEGFR-2) was determined by qRT-PCR and immune-histo chemistry.

Using three different donors 0.5-1.5% of total HDPSCs population was characterized as STRO_1+/CD45- cells at each time point cells cultured as mono layer in EGM-2 with VEGF showed up regulation of CD31 and VEGFR-2 expression compared to the control group while expression of CD34 and vWF remained unaffected . however on matrigel, all four genes were up regulated to different extents. CD31 and VEGFR-2 were up regulated to a greater degree compared to CD34 and vWF. Changes in gene expression in both cell types were time dependent. Immune-histochemical staining confirmed that the HDPSCs cultured in th test group showed positive staining for the four angiogenic markers ( CD31, CD34, vWF and VEGFR-2) when grown in both mono layer and 3D matrigel culture compared to control cultures. When cultured on matrigel ( but not monolayer) for 7 days, HDPSC formed tube like structures in the VEGF treated group.

This indicates the potential (currently under experimental research) of use HDPSCs and their STRO-1 positive population for angiogenesis to enhance skeletal tissue repair and/or regeneration toward translational research for clinical benefit.


Mesenchyamal dental stem cells in regenerative dentistry

Journal section: Biomaterials and Bioengineering in Dentistry

Doi: 10. 4317 medoral 17925

Mesenchymal Dental Stem cells derived from teeth are easily accessible multipotent cells with the capacity to differentiate into distinct cell types. This new source of stem cells could be of benefit in cellular therapy and the eventual development of techniques for use in regenerative dentistry and degenerative diseases.


Role of mesenchymal stem cell therapy in Crohn's disease

Jignesh Dalal, Kimberly Gandy & Jos Domen
Pediatric Research (2012) 71, 445-451 doi: 10.1038/pr.2011.56
08 February 2012

Many trials of mesenchymal stem cells (MSCs) have been published in the past 5-6 y. MSCs inhibit T-cell alloreactivity in vitro by soluble factors and direct cell-to-cell contact. They are safe to infuse in humans with no acute toxicity and no ectopic tissue formation. Promising results of MSC infusion for graft-vs-host disease and fistulizing Crohn's disease (CD) have been published. Treatment of CD requires a comprehensive treatment approach to maintain Symptomatic control, improve health-related quality-of-life measures, and minimize complications from the disease. In this review, we will discuss the results of clinical trials using a novel treatment in the form of MSCs for treatment of CD and related complications. Success of these phase l, ll and lll trials have set the stage for usage of this novel treatment for children with CD.


The current and future Therapies of Bone Regeneration to Bone Repair Defects

International Journal of Dentistry
Volume 2012, Article ID 148261, 7 pages

Eijiro Jimi,1.2 Shizu Hirata , 3Kenji Osawa,1 Masamichi Terashita,4
Chiaki Kitamura,2.3 and Hidefumi Fukushima 1

Bone defects often result from tumour resection, congenital malformation, trauma, fractures, surgery, or periodontitis in dentistry. Although dental implants serve as an effective treatment to recover mouth function from teeth defects, many patients do not have the adequate bone volume to build an implant. The gold standard for the reconstruction of large bone defects in the use of autogeneous bone grafts. While autogeneous bone grafts is the most effective clinical method, surgical stress to the part of the bone being extracted and the quantity of extractable bone limit this method. Recently mesenchymal stem cell-based therapies have the potential (currently under experimental research) to provide an effective treatment of osseous defects.

Although regenerative medicine has been tried in various fields, there is much demand for regenerative medicine in dentistry, particularly in bone regeneration. Depending on the state of periodontitis or jaw resection, it might take more than 6 to 12 months for occlusal reconstitution. Thus, the development of an efficient and high-quality bone derivation method is necessary. Cell-based therapy pave the way to rejection-free regenerative treatment for bone defects.


Stem cell therapy in oral and maxillofacial region: An Overview

Journal of Oral and Maxillofacial Pathology
Vol 16 issue 1 Jan – apr 2012 58

Sunil PM, Manikandan R 1, Muthu MS2, Abraham S3

The advantages of stem cells from oral and maxillofacial region is that

1. Have high plasticity. 2. It can be cryopreserved for longer period (Ideal for stem cell banking). 3. It showed good interaction with scaffold and growth factors. 4. Stem cells transplantations can cause pathogen transmission and also need immunosuppression, so autologous stem cell source is the best option. Dental pulp stem cells will be better fitting tool due to easy surgical access, the very low morbidity of the anatomical site after the collection of the pulp.[17]


Human Dental Pulp-Derived Stem Cells Promote Locomotor Recovery after Complete Transection of the Rat Spinal Cord by Multiple Neuro-Regenerative Mechanisms

PRC/D/2012/Jan 1

Kiyoshi Sakai, Akihito Yamamoto

Department of Oral and Maxillofacial Surgery, Department of Biochemistry, and Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Spinal cord injury (SCI) often leads to persistent functional deficits due to loss of neurons and glia and to limited axonal regeneration after injury. Here we report that transplantation of human dental pulp stem cells into the completely transected adult rat spinal cord resulted in marked recovery of hind limb locomotor functions. Transplantation of human bone marrow stromal cells or skin-derived fibroblasts led to substantially less recovery of locomotor function. The human dental pulp stem cells exhibited three major neuroregenerative activities. First, they inhibited the SCI-induced apoptosis of neurons, astrocytes, and oligodendrocytes, which improved the preservation of neuronal filaments and myelin sheaths. Second, they promoted the regeneration of transected axons by directly inhibiting multiple axon growth inhibitors, including chondroitin sulfate proteoglycan and myelin-associated glycoprotein, via paracrine mechanisms. Last, they replaced lost cells by differentiating into mature oligodendrocytes under the extreme conditions of SCI. Our data demonstrate that tooth-derived stem cells may provide therapeutic benefits for treating SCI through both cell-autonomous and paracrine neuroregenerative activities.


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